Outcomes are poor for patients with recurrent / metastatic squamous cell carcinoma of the head and neck ( SCCHN ), and new treatments are needed.
An ongoing phase I/II, multicenter, open-label study is evaluating the safety and efficacy of MEDI4736, a human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80 with high affinity and selectivity, in multiple solid tumor types including SCCHN. PD-L1 is expressed in SCCHN tumors and may be associated with response to anti-PD-L1 treatment.
Patients with recurrent / metastatic SCCHN, an ECOG of 0 or 1, without prior anti-PD-1/PD-L1 exposure are eligible.
MEDI4736 is administered IV every 2 weeks at 10 mg/kg for 12 months. Retreatment is permitted upon progression after 12 months.
PD-L1 expression is assessed by IHC using the Ventana SP263 clone.
Prior documented HPV status is collected at study entry.
Response is based on investigator assessment per RECIST v1.1.
A total of 62 patients ( mean age 58 years [ range 24–96 ]; 86% male; 64% current / prior smokers; ECOG 0/1: 38%/62%; HPV positive / negative / unknown: 40%/39%/21% ), with a median of 3 prior systemic treatments ( 1–10 ), received a median of 6 doses ( 1–26 ).
Drug-related adverse effects were observed in 60% of patients; the most frequent were fatigue ( 11% ), diarrhea ( 8% ), and nausea ( 7% ).
Grade greater than or equla to 3 related adverse effects were reported in 7% of patients: rash ( 2 pts ), and increased GGT ( gamma-glutamyltransferase ), fatigue, and tumor inflammation ( 1 pt each ).
No drug-related adverse reactions led to discontinuation or death.
No colitis or grade greater than or equal to 3 pneumonitis was observed.
Overall, 51 patients were evaluable for response with greater than or equal to 24 weeks of follow up; ORR [ overall response rate ] was 12% ( 25% in PD-L1+ patients ), and DCR [ disease control rate ] at 24 weeks was 16% ( 25% in PD-L1+ patients ).
Responses are ongoing in 5/6 responding patients, with response durations ranging from 4+ to 43+ weeks. Median duration of response has not been reached.
In conclusion, with more mature follow up, the safety profile of MEDI4736 in squamous cell carcinoma of the head and neck is manageable and consistent with previous reports.
Responses are durable; ORR and DCR are higher in PD-L1+ patients. ( Xagena )
Howard Segal N el al, J Clin Oncol 33, 2015 (suppl; abstr 3011)